소아 심장이식 후 림프증식성 질환의 진단을 위한 Epstein-Barr Virus 정량 검사의 유용성
Clinical Utility of Epstein-Barr Viral Load Assay to Diagnose Posttransplant Lymphoproliferative Disorders in Pediatric Heart Transplant Recipients
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목적: 소아 심장이식 환자에서 림프증식성 질환(posttransplant lymphoproliferative disorder [PTLD]) 발생과 Epstein-Barr virus (EBV) 정량값의 상관관계를 분석하고, PTLD의 발생에 영향을 주는 인자들에 대해서 알아보고자 하였다. 방법: 2006년 1월부터 2015년 3월까지 최근 9년간 서울아산병원 어린이병원에서 심장이식을 받은 18 세 미만 환자 중 이식 후 최소 1개월 이상 추적 관찰이 가능한 경우를 대상으로 후향적으로 의무기록을분석하였다. 결과: 총 40명의 심장이식 환자의 진단 시 나이의 중앙값은 11.5세(범위, 0.3–17.8세)였으며 이 중 3 명에서 이식 후 4.3개월, 6.3개월 및 17개월째 PTLD가 발생하였다. 이식 후 혈중 EBV 정량 검사를 시행한 28명 중 최소 1회 이상 EBV 바이러스혈증이 관찰된 경우는 7명이었으며, PTLD로 진단받은 환자3명이 모두 ≥10,000 copies/mL의 EBV 바이러스혈증이 선행되어 있었다. PTLD 발생군은 PTLD 비발생군에 비해 어린 나이에 이식을 받았으며(P =0.021), 초기 및 최고 혈중 EBV 역가가 더 높은 경향을 보였으나 통계적인 차이는 없었다. 결론: 소아 심장이식 환자에서 이식 당시 어린 연령 및 이식 후 EBV 바이러스혈증 동반 여부가 PTLD 발생과 관련이 있었다. 추후 전향적인 연구를 통해서 소아 심장이식 환자에서 PTLD 발생을 적절히예측할 수 있는 EBV 정량값의 지표를 구하는 것이 필요하겠다 .
Abstract
Purpose: The aim of this study was to investigate the risk factors for posttransplant lymphoproliferative disorder (PTLD) and to evaluate the association between Epstein-Barr viral load and the development of PTLD in pediatric heart transplant recipients. Methods: We reviewed children aged <18 years who underwent heart transplantation and quantitative analysis of blood Epstein-Barr virus (EBV) viremia at our institute from January 2006 to March 2015. Clinical characteristics and EBV viral loads were compared according to the presence of PTLD. Results: Over 9 consecutive years, a total of 40 heart transplant recipients, were included. Among 28 children with available EBV viral load measurements, seven patients (25%) had EBV viremia only defined as at least one time of ≥457 copies/mL. PTLD occurred in three recipients (7.5%) 4.3, 6.3, and 17.0 months after transplant and all PTLD cases had preceding EBV viremia. The median age at transplant was 5.3 years (range, 0.5 to 6.0 years) in the PTLD group, compared with 11.9 years (range, 0.3 to 17.8 years) in the non-PTLD group (P =0.021). The median values of the peak EBV levels in the PTLD group were 3,452,170 copies/mL (range, 46,750 to 7,622,910 copies/mL); the peak EBV levels in the non-PTLD group were 3,112 copies/mL (range, 2,250 to 103,000 copies/mL). Conclusions: Younger age at transplant and presence of EBV viremia were associated with the development of PTLD in pediatric heart transplant recipients. A prospective study will be required to determine the blood EBV load for predicting the development of PTLD in these patients.
참고문헌 (23)
- Timms JM, "Target cells of Epstein-Barr-virus(EBV)-positive post-transplant lymphoproliferative disease : similarities to EBV-positive Hodgkin's lymphoma", Lancet, 361, pp.217~223 (2003)
- Dharnidharka VR., "Post-transplant lymphoproliferative disorders", pp.17~28 (2010), Springer-Verlag
- Webber SA, "Lymphoproliferative disorders after paediatric heart transplantation : a multi-institutional study", Lancet, 367, pp.233~239 (2006)
- Wiesmayr S, "Post-transplant lymphoproliferative disorders", pp.163~172 (2010), Springer-Verlag
- Green M, "CMV-IVIG for prevention of Epstein Barr virus disease and posttransplant lymphoproliferative disease in pediatric liver transplant recipients", Am J Transplant, 6, pp.1906~1912 (2006)
- Lee TC, "Quantitative EBV viral loads and immunosuppression alterations can decrease PTLD incidence in pediatric liver transplant recipients", Am J Transplant, 5, pp.2222~2228 (2005)
- Bakker NA, "Presentation and early detection of post-transplant lymphoproliferative disorder after solid organ transplantation", Transpl Int, 20, pp.207~218 (2007)
- 서세영, "학령 전기 소아에서 거대세포바이러스IgG 항체 양성률의 변동", Korean Journal of Pediatrics, 49(1), pp.51~55 (2006), 대한소아과학회
- 손근형, "Clinical features of Epstein-Barr virus-associated infectious mononucleosis in hospitalized Korean children", Korean Journal of Pediatrics, 54(10), pp.409~413 (2011), 대한소아과학회
- International Agency for Research on Cancer, World Health Organization. WHO classification of tumours of haematopoietic and lymphoid tissues, "Swerdlow SH", International Agency for Research on Cancer, ~ (2008)
- Katz BZ, "Case-control study of risk factors for the development of post-transplant lymphoproliferative disease in a pediatric heart transplant cohort", Pediatr Transplant, 11, pp.58~65 (2007)
- Hanto DW, "Clinical spectrum of lymphoproliferative disorders in renal transplant recipients and evidence for the role of Epstein-Barr virus", Cancer Res, 41(11 Pt 1), pp.4253~4261 (1981)
- Frizzera G, "Polymorphic diffuse B-cell hyperplasias and lymphomas in renal transplant recipients", Cancer Res, 41(11 Pt 1), pp.4262~4279 (1981)
- Luskin MR, "The impact of EBV status on characteristics and outcomes of posttransplantation lymphoproliferative disorder", Am J Transplant, 15, pp.2665~2673 (2015)
- Mynarek M, "Posttransplant lymphoproliferative disease after pediatric solid organ transplantation", Clin Dev Immunol, 2013, pp.814973~ (2013)
- Cho YU, "Pattern analysis of Epstein-Barr virus viremia and its significance in the evaluation of organ transplant patients suspected of having posttransplant lymphoproliferative disorders", Am J Clin Pathol, 141, pp.268~274 (2014)
- Yancoski J, "Quantification of Epstein-Barr virus load in Argentinean transplant recipients using real-time PCR", J Clin Virol, 31, pp.58~65 (2004)
- Hayden RT, "Multicenter comparison of different real-time PCR assays for quantitative detection of Epstein-Barr virus", J Clin Microbiol, 46, pp.157~163 (2008)
- Preiksaitis JK, "Interlaboratory comparison of epstein-barr virus viral load assays", Am J Transplant, 9, pp.269~279 (2009)
- Thorley-Lawson DA, "Persistence of the Epstein-Barr virus and the origins of associated lymphomas", N Engl J Med, 350, pp.1328~1337 (2004)
- Green M, "Predictive negative value of persistent low Epstein-Barr virus viral load after intestinal transplantation in children", Transplantation, 70, pp.593~596 (2000)
- Walker RC, "Pretransplantation assessment of the risk of lymphoproliferative disorder", Clin Infect Dis, 20, pp.1346~1353 (1995)
- Manez R, "Posttransplant lymphoproliferative disease in primary Epstein-Barr virus infection after liver transplantation : the role of cytomegalovirus disease", J Infect Dis, 176, pp.1462~1467 (1997)